TY - DATA T1 - Supplementary Material for: Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma PY - 2016/04/16 AU - Nakahara Y. AU - Yamasaki M. AU - Sawada G. AU - Miyazaki Y. AU - Makino T. AU - Takahashi T. AU - Kurokawa Y. AU - Nakajima K. AU - Takiguchi S. AU - Mimori K. UR - https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Downregulation_of_SIRT4_Expression_Is_Associated_with_Poor_Prognosis_in_Esophageal_Squamous_Cell_Carcinoma/5129743 DO - 10.6084/m9.figshare.5129743.v1 L4 - https://ndownloader.figshare.com/files/8718316 KW - Esophageal squamous cell carcinoma KW - SIRT4 KW - Glutamine metabolism KW - Prognostic marker KW - Distant recurrence N2 - Objective: SIRT4, a mitochondria-localized sirtuin, represses glutamine metabolism by inhibiting glutamate dehydrogenase (GDH). The current study aimed to evaluate the clinical and biological significance of SIRT4 in esophageal squamous cell carcinoma (ESCC). Methods: The study comprised 172 patients with surgically resected ESCC in two independent cohorts. SIRT4 mRNA expression was analyzed in Cohort 1 (n = 79) and SIRT4 protein expression in Cohort 2 (n = 93). The association of SIRT4 expression with clinicopathological parameters and prognosis was assessed. Furthermore, the biological role of SIRT4 in ESCC cell lines was examined. Results: SIRT4 expression was not correlated with any clinicopathological parameters in both cohorts. In Cohort 1, low-SIRT4-expression cases had poorer overall survival than high-SIRT4-expression cases (p = 0.016). In Cohort 2, SIRT4-negative cases had poorer overall survival and disease-free survival than SIRT4-positive cases (p = 0.011 and 0.0026). Multivariate analysis revealed that SIRT4 expression was an independent prognostic factor for overall survival (HR = 2.06, p = 0.038). The rate of distant recurrence was significantly higher in SIRT4-negative cases than in SIRT4-positive cases (39.4 vs. 7.4%; p = 0.0023). In vitro, SIRT4 knockdown significantly increased GDH activity and promoted cell proliferation and migration. Conclusion: SIRT4 is a potential prognostic biomarker in ESCC. ER -